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IntroductionMucositis induced by anti-neoplastic drugs is an important, dose-limiting and costly side-effect of cancer therapy.AimTo evaluate the effect of the topical application of S-nitrosoglutathione (GSNO), a nitric oxide donor, on 5-fluorouracil (5-FU)-induced oral mucositis in hamsters.Materials and MethodsOral mucositis was induced in male hamsters by two intraperitoneal administrations of 5-FU on the first and second days of the experiment (60 and 40 mg/kg, respectively) followed by mechanical trauma on the fourth day. Animals received saline, HPMC or HPMC/GSNO (0.1, 0.5 or 2.0 mM) 1 h prior to the 5-FU injection and twice a day for 10 or 14 days. Samples of cheek pouches were harvested for: histopathological analysis, TNF-α and IL-1β levels, immunohistochemical staining for iNOS, TNF-α, IL-1β, Ki67 and TGF-β RII and a TUNEL assay. The presence and levels of 39 bacterial taxa were analyzed using the Checkerboard DNA-DNA hybridization method. The profiles of NO released from the HPMC/GSNO formulations were characterized using chemiluminescence.ResultsThe HPMC/GSNO formulations were found to provide sustained release of NO for more than 4 h at concentration-dependent rates of 14 to 80 nmol/mL/h. Treatment with HPMC/GSNO (0.5 mM) significantly reduced mucosal damage, inflammatory alterations and cell death associated with 5-FU-induced oral mucositis on day 14 but not on day 10. HPMC/GSNO administration also reversed the inhibitory effect of 5-FU on cell proliferation on day 14. In addition, we observed that the chemotherapy significantly increased the levels and/or prevalence of several bacterial species.ConclusionTopical HPMC/GSNO accelerates mucosal recovery, reduces inflammatory parameters, speeds up re-epithelization and decreases levels of periodontopathic species in mucosal ulcers.

Injectable facial fillers are excellent options for treating facial aging, wrinkles, and contour defects. Both polycaprolactone (PCL) and hyaluronic acid (HA) have been used to restore lost tissue volume and improve facial contour. However, the mechanisms involved in the effect of these biomaterials still need to be fully understood. The present work aims to establish an experimental model to investigate cellular and morphological changes in the skin of Wistar rats in response to HA and PCL to understand the mechanisms associated with these effects. The subcutaneous tissue of the back of Wistar rats was used as a reception area for biomaterials, represented by the commercial products Ellansé®, containing polycaprolactone (PCL) and Juvederm Voluma®, containing hyaluronic acid (HA). Animals were euthanized afetr 30 or 60 days, and skin samples were collected from treated and untreated animals (CONTROL) for histological and immunohistochemical evaluation for IBA-1, TGF-β, and FGF. Analysis of type I and type III collagen deposition, neovascularization, and adipose tissue was performed. On histological examination, HA appeared as an amorphous, basophilic material interspersed with connective tissue bundles. The skin fragments with PCL showed intense cell proliferation, with foreign body giant cells and a higher capillary proliferation than the HA group. More vessels were observed in the HA and PCL groups compared to the CONTROL group. A significant increase in fibroblasts and fibrocytes was observed in skin fragments inoculated with HA and PCL, associated with increased FGF expression. The number of fibroblasts was significantly higher in the PCL group than HA. The PCL group showed higher immunostaining for IBA-1 and TGF-β than the CONTROL and HA groups. Collagen deposition was observed in the treated groups, especially type III collagen in the PCL group, when compared to HA. Our morphological results demonstrated stimulation of fibroblastic activity and active-related tissue regeneration, with increased vascular proliferation and expression of markers related to tissue proliferation, mainly associated with the PCL group. We also observed increased adipose tissue, although further studies are needed to confirm these findings.